The study was initiated to evaluate the mechanisms of action of polypeptide growth factors on epithelial cells of human and murine origin. The effects of epidermal growth factor (EGF) were found to be dose-dependent, dependent on the number of cell surface receptors, and they were reversible. EGF stimulates plasma membrane mobility and macropinocytosis and, concomitantly, enhances cell proliferation. The cell surface changes are sensitive indicators of the regulatory effects EGF exerts on epithelial cells. Our comparative studies indicate that epithelial cells of different origin respond differently to the growth factor. Although the receptor-rich human carcinoma cells of line A431 react immediately and intensively to EGF, the response of nontransformed murine cells (line MMC-E) results exclusively in a series of well defined morphologic events. Thus, these cells are especially well suited for the study of the effects of various growth factors and, furthermore, may serve as a model for the study of plasma membrane motility. Our results provide a basis for further studies in this research area.